DESCRIPTION: (Investigator's Abstract). The ocular lens is an avascular, semisolid organ whose function is to refract incoming light upon the retina. Concomitant with this function is a necessity for the lens to remain transparent. A loss of transparency of the lens is usually permanent and is termed a cataract. Cell and organ functions, such as obtaining nutrients necessary for maintaining the healthy, transparent lens state, for handling of cell waste removal, and for maintenance of overall membrane stability are carried out through select and specific proteins or groupings of proteins within the lens cell membrane. Proper controls on expression of these proteins and their subsequent function is essential for lens survival, and maintenance of transparency. The mechanisms regulating these membrane proteins in the lens are presently unknown. The goal of this project is to understand the regulation of the lens fiber cell membrane protein MP19 gene (LIM2). To achieve this goal, the P.I. will investigate the following topics: a). To characterize the mouse To3 cataract mutant and the human congenital nuclear cataract and their relationship to the lens membrane LIM2 gene. Using transgenic mouse technology to mimic the To3 cataract in order to study the function of MP19. b). To determine the region(s) responsible for transcriptional activity of the human LIM2 gene (cis elements), using CAT reporter gene constructs in transient transfection assays. c). Identify protein:DNA interactions (trans factors) associated with the LIM2 basal promoter region and upstream cis elements using gel mobility shift and DNA foot printing procedures. d). To investigate the methylation patterns of LIM2 upstream regions to determine if methylation of critical cis elements serves to control LIM2 gene function. These studies will give a better understanding of the role of MP19 in the maintenance of lens transparency and its possible role in cataract formation.